Promoter methylation of cancer-related genes in gastric carcinoma

Genetic changes associated with gastric cancer are not completely known, but epigenetic
mechanisms involved in this disease seem to play an important role in its pathophysiology.
One of these mechanisms, an aberrant methylation in the promoter regions of genes involved
in cancer induction and promotion, may be of particular importance in gastric cancer. Aim:
To analyze the methylation status of eight genes: Apaf-1, Casp8, CDH1, MDR1, GSTP1, BRCA1,
hMLH1, Fas in gastric cancer patients. Methods: The methylation pattern of the genes was
assessed by methylation specific restriction enzyme PCR (MSRE-PCR) in gastric tumors taken
during surgery of 27 patients and compared with the methylation pattern in material
obtained from biopsy in 25 individuals without cancer and pre-cancerous lesions. Results:
We observed a promoter hypermethylation in the Casp8, hMLH1, CDH1 and MDR1 in gastric
cancer patients as compared with the controls. Additionally, we investigated the
relationship between promoter hypermethylation and age, gender, smoking and gastric cancer
family history. The hypermethylation of the hMLH1 gene occurred more frequently in female
than in men, and the hypermethylation of the CDH1 gene was observed preferentially in
smoking than in non-smoking individuals. Conclusion: The data obtained indicate that
changes in DNA methylation may contribute to gastric carcinogenesis.